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Biomedical subjects

E Polard

Publications and source records attributed to E Polard.

11 recordsLinked to original sources

[Myoclonic encephalopathy associated with proton pump inhibitors].

Two men (66 and 73 Years) with a cardiovascular history were hospitalized for rapid onset encephalopathy associated with myoclonia and an extrapyramidal syndrome. On the basis of the French Pharmacovigilance system, this symptomatology has been attributed to the coadministration of a proton pump inhibitor, lansoprazole (15mg/day) with levodopa. Lansoprazole withdrawal led to a normalisation of the situation.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[Mechanisms of chronic cough pathophysiology].

INTRODUCTION: In some situations such as post-virus or post whooping cough, a non productive subacute cough may occur without apparent local inflammation, epithelium abnormalities or bronchoconstriction. This subacute or chronic cough represents a real syndrome (cough disease) due to the central nervous system (CNS) and its ortho and parasympathic outputs. At the CNS level, functional disturbancies and neosynaptogenesis can be described, with the intervention of the NMDA-type glutamatergic receptors. STATE OF ART: The neurons located in the expiratory area of the breathing center (Pre-Boetzinger complex of the lower brainstem) present exagerated responses to stimuli, due to the repetitive stimulation of the NMDA receptors; this phenomenon is similar to long-term-potentiation (LTP), the molecular basis of learning, memory and neosynaptogenesis. The cough reflex is thus amplified and rapidly chronic and would justify any pharmacological intervention at the NMDA-receptors level. PERSPECTIVES: More recently 5TH4 receptors have been implied in the control of respiration; an overexpression of these receptors in the Pre-Boetzinger area could contribute to an increase of the cough reflex. CONCLUSION: The present review aims at summarizing the main rationale target to pharmacologically block the chronic cough.

Antitussive Agents↗

[Perspectives for drug treatment in Alzheimer's disease].

The last decade was very fruitful in neuropharmacology and notably in the therapeutic strategies of dementia and Alzheimer's disease (AD). The amount of data, information and breakthroughs is nevertheless difficult to apply in direct relationship with patients. The present review aims at classifying information according to their origins: epidemiology, clinical trials, neurosciences. A guide for drug prescription in Alzheimer's disease is thus warranted and becomes clearer, sure that, in the next future modifications and new strategies will appear. The main goal of the present review is to summarize the state-of-the-art for a non specialist in AD.

Alzheimer Disease↗

Non steady state and steady state PKS Bayesian forecasting and vancomycin pharmacokinetics in ICU adult patients.

The pharmacokinetics of vancomycin was investigated in adult ICU patients after the first administration and at steady state. Then the predictive performance of a two-compartment Bayesian forecasting program was assessed in these patients by using population-based parameters and three non steady state vancomycin concentrations as feedback information. Finally a prospective investigation was carried out to search potential covariates. At steady state, a significant decrease (around 30%) in clearance (CL) was observed, while creatinine clearance (CLcr) was stable and a significant increase (around 30%) in volume of distribution (V(SS)) was observed. A two-fold increase in elimination half-life was found. CL was weakly correlated with CLcr at onset of therapy and at steady state. The Bayesian program tended to overpredict vancomycin peak and trough concentrations. A larger mean prediction error and a poorer precision were observed when population-based parameter estimates were used (no feedback) compared to feedback prediction, but the differences were not significant. Mechanical ventilation and concurrent opioid therapy may be pertinent covariates of vancomycin pharmacokinetics. The current work has shown that vancomycin pharmacokinetics in ICU patients displayed a significant variability and a significant change in both clearance and distribution during the course of therapy. Further investigation is necessary to clarify these findings. Moreover, the use of the Bayesian forecasting PKS program in our patients led to a prediction with low bias but rather poor precision. This outcome highlights the need to implement a population modeling approach, to determine the vancomycin pharmacokinetic parameters and covariates in our ICU patients, and to apply this information to provide more accurate concentration predictions.

Adolescent↗

[Disulone and hepatosiderosis].

BACKGROUND: Disulone (dapsone + iron oxalate) is a sulfone used in the treatment of numerous skin diseases. We report two cases of hepatosiderosis secondary to long-term administration of Disulone. PATIENTS AND METHODS: Case n degrees 1. A 51-year-old man was treated with Disulone for a neutrophilic skin disease. After 17 years of treatment, elevated serum ferritin and free iron with hemolysis were found. Liver biopsy confirmed hepatosiderosis. A diagnosis of genetic hemochromatosis was ruled out by the absence of C282Y mutation of the HFE gene. Case n degrees 2. A 52-year-old man receiving Disulone for dermatitis herpetiformis for 25 years presented elevated serum ferritin and free iron with hemolysis. Hepatic iron overload was confirmed by liver biopsy. The absence of C282Y mutation (HFE gene) ruled out a diagnosis of genetic hemochromatosis. DISCUSSION: In our two cases, hepatosiderosis was noted after long-term administration of Disulone. This complication has been reported only rarely. In murine models, a relationship was found between prolonged administration of dapsone and hepatic iron overload as revealed by hemolysis. Although it is difficult to extrapolate this relationship to humans with any certainty, our patients had also chronic hemolysis and iron overload secondary to administration of Disulone. Moreover in France, dapsone is marketed in combination with iron oxalate, with the attendant risk of iron overload. These cases raise the question of the need for serum ferritin analysis during Disulone therapy.

Anti-Inflammatory Agents, Non-Steroidal↗

[Adverse effects and drugs for Alzheimer's disease].

Molecules currently available or in late phases of development for the treatment of Alzheimer's disease have modest and apparently equivalent efficacies. Thus, the choice will depend on the safety profile of these drugs and on the patient characteristics. The aim of this review is to undertake an inventory of adverse effects and interactions reported in the literature for anticholinesterasics (the only ones approved by authorities). As most of the molecules described in this article are still in early phases of development, data reported here mainly issued from clinical trials carried out on specific populations. Most of these reported adverse effects have not been attributed according to the rules of pharmacovigilance. Nevertheless, we believe that the data presented in this review will be of great interest to clinicians and pharmacovigilance specialists as the compounds concerned become available on the market.

Alzheimer Disease↗

[Acting out and psychoactive substances: alcohol, drugs, illicit substances].

In humans, some psychotropic agents (alcohol, drugs, illicit substances) have been suggested to play a role in the occurrence of major behavioural disorders, mainly due to the suppression of psychomotor inhibition. Behavioural disinhibition is a physiological mechanism which allows humans to behave appropriately according to a given environmental situation. The behavioural disinhibition induced by either therapeutic dosage or misuse involves the loss of restraint over certain types of social behaviour and may increase the risk of auto or hetero-aggression and acting out. The increased use of psychotropic agents in recent years and the occurrence of unwanted effects are worrying and must be detected and evaluated. The objective of the present study was to establish a causal relationship between psychoactive substance use and occurrence of major behavioural disorders, such as paradoxical rage reactions and suicidal behaviour, based on a literature analysis. It consisted of reviewing reports of drug-induced violent reactions in healthy volunteers and demonstrating, where possible, a cause-effect relationship. Patients with schizophrenia and psychopathic personalities were not included in our study since psychiatric comorbidity could influence behavioural responses. Psychotropic agents included drugs, licit and illicit substances already associated with violence in the past. Many reports used the "Go/No Go test" to evaluate the disinhibiting effect of psychotropic substances; this allows the "cognitive mapping" of drugs. The results suggest that only alcohol, antidepressants, benzodiazepines and cocaïne are related to aggressive behaviour. The best known precipitant of behavioural disinhibition is alcohol, which induces aggressive behaviour. However, there are large differences between individuals, and attentional mechanisms are now recognised as being important in mediating the effects of alcohol. Suicidal tendency as an adverse antidepressant reaction is rare, especially with atypical antidepressants. However, the risk of acting out exists and the responsibility of antidepressant agents in the genesis of suicidal tendencies is now established. The disinhibiting effects of benzodiazepines are well-known and proven by clinical trials. It's a "model" of acting out, and the causal relationship is undeniable. That cocaïne is related to violent behaviour is demonstrated by its pharmacological actions on CNS. The chronic use of cocaïne induces "a limbic dyscontrol syndrome" based on the altered activity of limbic structures. On the contrary, we could not demonstrate a causal relationship between aggression and either cannabis, ecstasy or phencyclidine. Cannabis abusers look particularly for euphoria and relaxing effects. Aggression as an adverse cannabis reaction is very rare and occurs in most cases in association with other drugs and in predisposed individuals. Ecstasy use may lead to long-term alterations of neuronal function in the human CNS and cause psychiatric disorders. However, there is insufficient information about long-term use of ecstasy to estimate its role in the occurrence of behavioural disorders. Clinical and forensic assumptions about phencyclidine and violence were not warranted. However, the substance-effect relationships can be criticized in the case of alcohol, antidepressants, benzodiazepines and cocaïne. In fact, individual, social and psychiatric factors exert an influence on behaviour that is superior to the pharmacological effect of psychotropic agents. The most important parameter in drug-induced behavioural disinhibition is dosage, but mode of administration is also important. In addition, polysubstance abuse is very common. Substances may be taken simultaneously and alcohol is frequently combined with drugs. The combinations of substances result in multiple interactions, and very little is known about the effects of these interactions on violence in humans. Co-occurrence of substance abuse and other mental disorders is also very frequent. Multiple substance abuse should be avoided, because potential interactions between two or more drugs are more likely to cause violent behaviour. In the future, a specific treatment of these deleterious phenomena will have to be considered in order to reduce drug-induced iatrogenic behavioural disorders.

Alcoholism↗

[Drug distribution systems in hospitals].

Any drug generally made and marketed by drug companies must respect the quality standards conferred by New Drug Approval regarding both safety and efficacy. Once prescribed by a doctor, inside a hospital, the drug, or more precisely the decision of its prescription will follow a complex circuit, involving numerous intermediates (human and technical) leading to drug dispensation and follow-up. Regulatory guidelines and rules harmonise and standardise this drug pathway in hospitals. Any weakness in this distribution system will be the source of nosocomial drug iatrogeny. The present review aims at describing the different steps and stages from the prescription to an individual patient to drug administration and follow-up. The evaluation of this system will be mentioned in the perspective of optimisation. The computerised system is essential allowing tracking of a drug, and providing help for decision-making (by confrontation with data bases) and a research tool (i.e, pharmacoepidemiology). Different experiences of assessment of the performance of such a drug distribution system inside hospitals will be presented, trying to check the quality reference: the right drug, the right patient, the right moment, in good conditions. The challenge is to optimise and secure all steps of the process. This goal needs assessment and quality control of the different phases, opening the discussion between hospital policy and regulatory and technical considerations.

Device Approval↗